The overall objective of this project is to examine the metabolism of specific plasma protein mRNAs in the diabetic rat liver. Diabetes results in a significant decrease in the average production rate of total secretory proteins by the liver, with marked reduction in the relative rate of synthesis of albumin and its corresponding mRNA. However, diabetes also results in the apparent selective increase in certain plasma protein mRNAs, opposite to that of albumin mRNA. Administration of insulin restores these metabolic defects to normal, but the molecular nature of the involvement of this hormone is unknown. These changes in the production of plasma proteins do not appear to be the result of control at the translational level, but are related to the metabolism alterations in plasma protein mRNA levels in diabetes and subsequent insulin treatment. Specific cDNA hybridization probes to plasma protein mRNAs that increase and decrease in diabetes will be prepared and identified, and employed to characterize the observed metabolic changes. The relative rates of plasma protein gene transcription, the quantitative alterations in specific mRNA levels, and the relative degradation rates of these mRNAs will be investigated. Different physiological conditions will be examined to assess the role of insulin and glucagon in regulating plasma protein mRNA metabolism, and correlations will be made to the production and half-lives of the liver-derived plasma proteins.